Protein interactions in chromosomes are being studied with crosslinking reagents and chemotherapeutics agents. A method has been developed for isolating and characterizing protein crosslinked to DNA. Nitrogen mustard was found to crosslink certain nonhistone protein, and possibly one histone to DNA. Cis and trans-Pt(II) also cause extensive DNA-protein crosslinking. Cis and trans-Pt have different biological effects on lambda DNA as well as on mammalian cells. With trans-Pt (II), inactivation of lambda DNA is directly proportional to the number of molecules with interstrand crosslinks. With cis-Pt (II) the major lethal event is not interstrand crosslinks but probably an intrastrand lesion. Thiourea will reverse all Pt (II) induced lethal lesions. Histone-histone interactions are also being studied with crosslinking reagents. Water soluble carbodiimide crosslinks histones in chromosomes to one another, one major product being a H1-H2a dimer. Other products are being characterized to obtain some insight into histone-histone interactions.